National Rx Drug Abuse Summit, April 2-4, 2013, General Session presentation "Realities of Addiction," by Dr. Nora Volkow, Director, National Institute on Drug Abuse

1. Reali&es
of
Addic&on
Dr.
Nora
Volkow
April
2
–
4,
2013
Omni
Orlando
Resort
at
ChampionsGate

2. Learning
Objec&ves
1.
Iden=fy
recent
increasing
trends
in
the
misuse
and
abuse
of
prescrip=on
drugs.
2.
Describe
the
ways
in
which
the
most
commonly
abused
prescrip=on
drug
classes
affect
the
brain
and
body.
3.
Explain
strategies
being
developed
and
implemented
that
will
increase
awareness
of
the
growing
problem
of
addic=on.

3. Disclosure
Statement
• Dr.
Nora
Volkow
has
no
financial
rela=onships
with
proprietary
en==es
that
produce
health
care
goods
and
services.

4. Nora D. Volkow, M.D.
Director

5. Numbers in Millions
Prescrip&on
Drug
Misuse/Abuse
is
a
Major
Problem
in
the
US
Current
Drug
Use
Rates
in
Persons
Ages
12+
Source:
SAMHSA,
2011
Na2onal
Survey
on
Drug
Use
and
Health`

6. Prevalence of Past Year Drug Use Among 12th graders
2012 Monitoring the Future Study
* Nonmedical use
Drug
Prev.
Drug
Prev.
Tranquilizers*
5.3
Marijuana/Hashish
36.4
Hallucinogens
4.8
Small
Cigars
19.9
Seda&ves*
4.5
Hookah
18.3
Salvia
4.4
Synthe=c
Marijuana
11.3
OxyCon&n*
4.3
Snus
7.9
Hall
other
than
LSD
4.0
Narco2cs
o/t
Heroin*
7.9
MDMA
(Ecstasy)
3.8
Amphetamines*
7.9
Inhalants
2.9
Adderall*
7.6
Cocaine
(any
form)
2.7
Vicodin*
7.5
Ritalin*
2.6
Cough
Medicine*
5.6
LSD
2.4
Categories not mutually exclusive

7. 0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
Time After Amphetamine
%ofBasalRelease
AMPHETAMINE
0
50
100
150
200
0 60 120 180
Time (min)
%ofBasalRelease
Empty
Box Feeding
Di Chiara et al.
FOOD
VTA/SN
nucleus
accumbens
frontal
cortex
These prescription drugs,
like other drugs of abuse
(cocaine, heroin, marijuana)
raise brain dopamine levels
Dopamine
Neurotransmission
Why Do People Abuse Prescription Drugs?

8. Opioids: Examples: OxyContin, Vicodin
Attach to opioid receptors in the
brain and spinal cord, blocking
the transmission of pain messages
and causing an increase in the
activity of dopamine
How They Work…
• Postsurgical pain relief
• Management of acute or chronic
pain
• Relief of coughs and diarrhea
Opioids are Generally Prescribed for:
Amydala
(reward)
NAc
(reward)
Thalamus
(pain)

9. Similari&es
Between
Illicit
and
Prescrip&on
Drugs

10. Stimulants
Enhance brain activity by increasing the activity of
brain excitatory chemical messengers, such as
norepinephrine and dopamine, leading to mental
stimulation
Example: Ritalin
How They Work…
• ADHD
• Narcolepsy
• Depression that does not
respond to other treatments
• Asthma that does not
respond to other treatment
Stimulants Are Generally Prescribed For:

11. Methamphetami
ne
Adderall
Similari&es
Between
Illicit
and
Prescrip&on
Drugs

12. • Expectation of Drug Effects
Expectation of clinical benefits vs euphoria high
• Context of Administration
School, clinic, home vs bar, discotheque
• Dose and Frequency of Dosing
Lower, fixed regimes vs higher, escalating use
• Route of Administration
Oral vs injection, smoking, snorting
What is the Difference Between
Therapeutic Use and Abuse?

13. "High"
"High"
0
20
40
60
80
100
0
20
40
60
80
100
0 10 20 30 40 50 60 70 80
%Peak
[11C]Cocaine
Time (min)
[11C]Methylphenidate
0 10 20 30 40 50 60 70 80
Rewarding Effects Depend on How Fast
the Drug Gets into the Brain

14. 0
0.01
0.02
0.03
0.04
0.05
0.06
0 20 40 60 80 100 120
UptakeinStriatum(%/cc)
Time (minutes)
0
0.01
0.02
0.03
0.04
0.05
0.06
UptakeinStriatum(%/cc)
0
0.0005
0.001
0.0015
0.002
0.0025
0.003
0.0035
0 20 40 60 80 100 120
UptakeinStriatum(nCi/cc)
Time (minutes)
iv cocaine iv Ritalin oral Ritalin
Rate of Drug Uptake Into the Brain
Cocaine (iv) and Ritalin (iv) produce a high
but Ritalin (oral) does not.
The slow brain uptake of oral Ritalin
permits effective treatment without a high.
0 20 40 60 80 100 120
Time (minutes)
Fast!!!Fast!!! Slow!!!

15. Source:
Volkow,
ND
et
al.,
Journal
of
Neuroscience,
23,
pp.
11461-­‐11468,
December
2003.
Glucose
Metabolism
Was
Greatly
Increased
By
the
Expecta2on
of
the
Drug
Unexpected MP70
0
µmol/100g/min
Expected MP
Increases
in
Metabolism
Were
About
50%
Larger
When
MP
Was
Expected
Than
Unexpected
0
5
10
15
20
25
30
%Change
Unexpected
MP
Expected
MP
Expected
MP
Got
Placebo

16. What
Has
Raised
Our
AUen2on
to
the
Problem
of
Prescrip2on
Drug
Abuse?

17. Source: SAMHSA Treatment Episode Data Set
(TEDS), 2000-2010
28,326
37,649
45,882
52,664
60,824
71,048
82,359
98,386
122,185
142,124
157,171
0
20,000
40,000
60,000
80,000
100,000
120,000
140,000
160,000
180,000
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
More Than 5-Fold Increase
In Treatment Admissions For
Prescription Painkillers
In the Past Decade
12
10
8
6
4
2
0
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
*Deaths
are
those
for
which
poisoning
by
drugs
(illicit,
prescrip=on,
and
over-­‐the-­‐counter)
was
the
underlying
cause.
Drug
Overdose
Death
Rates
in
the
US
Have
More
Than
Tripled
since
1990
Na&onal
Vital
Sta&s&cs
System.
Drug
Overdose
Death
Rates
by
State
2008.
100
people
die
from
drug
overdoses
every
day
in
the
US

18. 35,00
0
30,00
0
25,00
0
20,00
0
15,00
0
10,00
0
5,000
0
Number
of
ED
Visits
9,000
6,000
3,000
0
Aged
5
to
11
Aged
12
to
17
Aged
18
to
25
Aged
26
to
34
Aged
35
or
Older
2005
2010
3,322
3,791
2,702
3,461
2,131
8,148
1,754
6,094
2,519
7,957
Number
of
ED
Visits
2005
2006
2007
2008
2009
2010
4,315
6,332
11,390
11,448
12,208
14,068
17,174
14,503
12,287
14,979
10,614
9,059
13,379
16,948
26,369
23,735
26,711
31,244
All
Males
Females
Emergency Department (ED) Visits Related to
Stimulant Medications
Source:
SAMHSA
Dawn
Report:Emergency
Department
Visits
Involving
AUen2on
Deficit/
Hyperac2vity
Disorder
S2mulant
Medica2ons
,
January
24,
2013.

19. Data in Several States Show That Hepatitis C Virus
Among Adolescents and Young Adults
Has Increased in Recent Years
Of
cases
with
available
risk
data,
injec2on
drug
use
(IDU)
was
the
most
common
risk
factor
for
HCV
transmission
Although
only
a
small
number
of
these
cases
responded
to
further
inves2ga2on…..
•
92%
reported
opioid
analgesic
abuse
•
89%
reported
heroin
use
•
95%
used
opioid
analgesics
before
switching
to
heroin
•
During
the
preceding
6
months,
the
most
frequently
injected
drugs
were
heroin
(50%)
and
opioid
analgesics
(30%)
CDC, MMWR, May 6, 2011/60(17); 537-541;CDC,
MMWR,
October
28,
2011/60(42):1457-­‐1458

20. Number of Opioid Prescriptions Dispensed by
U.S. Retail Pharmacies, Years 1991-2011
76 78 80
86 91 96 100
109
120
131
139
144
151
158
169
180
192
201 202
210
219
0
50
100
150
200
250
91
92
93
94
95
96
97
98
99
2000
01
02
03
04
05
06
07
08
09
10
11
Prescriptions(millions)
IMS’s Source Prescription Audit (SPA) &
Vector One®: National (VONA)
Opioids Hydrocodone Oxycodone

21. Oxycodone and Hydrocodone Prescriptions
1998-2012
Codeine & Comb NON-INJ (USC 02232), Morphine & Opium NON-INJ
(USC 0222), Morphine & Opium INJ (USC 02221), Codeine & Comb INJ
(USC 02231).
Source: SDI Health, VONA
16 19 22 25 27 29 31 34 38 43 47 49 54 57 57
72
83
90
96 101 106 110
120
126
132 133 130 131 136 134
0
20
40
60
80
100
120
140
160
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Millions
Oxycodone (Schedule II)
Hydrocodone (Schedule III)

22. Opioid Prescriptions
by Age
2
6
19
30
159
-
20
40
60
80
100
120
140
160
180
-
5
10
15
20
25
30
35
2002 2006 2009 2012
No.ofPrescriptions,Age40+(millions)
No.ofPrescriptions(millions)
0 to 9 10 to 19 20 to 29
30 to 39 40+
IMS Health, Vector One® National
Opioids Overdose
Death by Age Group,
US, 2008
Rate
per
100,000
Paulozzi LJ, J Safety Res 2012; 43(4):
283-289.

23. 20%
15%
11%
10%
9%
27%
12%
11%
8%
5%
20%
16%
11%
9%
6%
20%
13%
9%
8%
7%
16%
12%
7%
6%
3%
0
0.1
0.2
0.3
Percentage of Prescriptions Dispensed for Opioid Analgesics from
Outpatient US Retail Pharmacies, by Age Group
20062002
22%
16%
11%
10%
8%
27%
12%
11%
8%
5%
19%
18%
12%
8%
7%
24%
12%
10%
8%
7%
26%
17%
9%
7%
4%
0
0.2
0 to 9
10 to 19
20 to
29
30 to 39
≥40
EN Phys
Pediatrici
an
Dentist
Emerg
Med
GP/FM/
DO
Ortho
Surg
OB/GYN
Intern
Med
Anesthes
IMS Health, Vector One®
National
23%
16%
13%
11%
6%
29%
12%
8%
8%
6%
17%
16%
13%
8%
8%
21%
10%
9%
8%
7%
25%
16%
7%
6%
6%
-­‐10%
10%
30%
2012

24. Top Prescribers of Opioid Analgesics in
2012
0
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
20022003200420052006200720082009201020112012
Prescriptions
GP/FM/DO
Internal medicine
Dentistry
Orthopedic
Surgery
IMS Health, Vector One® National

25. Percent
Source:
2010
Na2onal
Survey
on
Drug
Use
and
Health,
SAMHSA
2011.
Source
of
Prescrip&on
Drugs
(how
they
obtained
the
drugs
they
most
recently
used
nonmedically)
Rates
averaged
across
2009
and
2010

26. Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659.
National Center for Health Statistics show drug overdose deaths
increased for the 11th consecutive year in 2010
In
2010,
there
were
38,329
drug
overdose
deaths
in
the
United
States
Percentage
of
Overdose
Deaths
for
Specific
Psychotherapeu=c
and
CNS
Pharmaceu=cals
that
Involved
a
Single
Drug
Class,
US,
2010
Psychotherapeuticand
CNSPharmaceuticals,%
Opioid
Analgesics
(n=16,651)
An&epilep&c
&
An&parkinsonism
Drugs
(n=1,717)
Benzodizepines
(n=6,497)
Barbiturates
(n=296)
An&depressants
(n=3,889)
An&psycho&c
&
Neurolep&c
Drugs
(n=1,351)
Other
Psychotropic
Drugs
(n=24)
35
30
25
20
15
10
5
0

27. Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659.
PERCENT
Drug
Involvement
in
Pharmaceu=cal
Overdose
Deaths
Opioid
Analgesic
Involvement
in
Deaths
for
Specific
Drugs
Specific
Drug
Involvement
in
Pharmaceu&cal
Overdose
Deaths
USA,
2010
75.2
7.8
29.4
1.3
17.6
6.1
0.1
100
65.5
77.2
50
57.6 58
54.2
0
20
40
60
80
100
120

28. How to Minimize the Diversion and
Abuse of Prescription Medications
Engage the Healthcare System

29. Doctors Need to Know…
What Opioid Prescriptions Have Been Given to
Their Patients By Other Doctors or Practitioners
This information should be:
1) included in the patients’
electronic health care records
2) accessible through a
Prescription Drug Monitoring
Program (PDMP) that provides
immediate information and can
cross-reference across States

30. Mezei,
L
and
Murinson,
BB.,
J
Pain,
12,
1199
-­‐1208,
2011.
Education on Pain in Medical Schools
Number of Hours of Pain Education
Number
of
Schools
USA (median: 7 hours)
Canada (median: 14 hours)
Veterinarian schools:
75 hours on pain
0-5 5-10 10-15 15-20 20-25 25-30 >30

31. • Centers of Excellence in Pain Education (12 CoEPE)
• Consensus Workshop on Opioids
for Chronic Pain
ICs Involved:
ORWH NIA
OBSSR NINR
NIDA NICHD
NIDCR NIAMS
NINDS NCCAM

32. • Efficacy of opioids for treating chronic pain
• How to administer opioids for optimal efficacy and minimal
adverse effects
• Risks for addiction
• Populations differences
• What training is available (other than offered by industry) for
teaching how and what type of opioids should be used in
managing chronic pain?
• What research directions need to be pursued to determine best
approaches for managing chronic pain with opioids?
• For research gaps, what are research priorities?
Consensus Workshop: Opioids for Chronic Pain

33. Prevention Strategies – Public Education
CME Courses developed by NIDA & Medscape Education, funded by ONDCP
Safe
Prescribing
for
Pain
Managing
Pain
Pa&ents
Who
Abuse
Rx
Drugs
Skills
and
tools
clinicians
can
use
to
screen
for
and
prevent
abuse
in
pa7ents
with
pain
Learn
symptoms
of
opioid
addic7on
and
dependence
in
pa7ents
with
chronic
pain,
and
how
to
screen
for,
prevent
and
treat
such
condi7ons

34. Pain
Medica&ons
• Develop medications with slower abuse
potential including drugs that don’t cross
BBB (i.e., CBR2 agonist)
• Develop slow release formulations (low
dose and long duration)
• Develop novel formulations to
reduce abuse liability including
mixture formulations (e.g., naloxone
and buprenorphine)
0
0.0005
0.001
0.0015
0.002
0.0025
0.003
0.0035
0 20 40 60 80 100120
UptakeinStriatum(nCi/cc)
Time (minutes)
Slow!!!

35. Prevention Strategies – Overdose Intervention
• Naloxone Distribution for opioid
overdose victims. The potential for
direct intervention to save lives.
• Naloxone Nasal Spray Development
Needle-free, unit-dose, ready-to-use
opioid overdose antidote
NIDA
STTR
Grantee
–
An7Op,
Inc.,
Daniel
Wermeling,
CEO
Contact:
E-­‐mail:
dpwermeling@gmail.com,
Tel:
859-­‐221-­‐4138

36. Treatment of Addiction to Prescription Opioids
Buprenorphine
Currently
19,000
physicians
are
certified
to
prescribe
buprenorphine
(Source:
CSAT
Buprenorphine
Information
Center)
Targets the same opioid receptors as
morphine (mu) but its much less potent,
has a much longer half life and does not
produce the same high as heroin or
morphine

37. Universal Drug Abuse Prevention
May Reduce Prescription Drug Misuse
Spoth et al., Addiction 2008;103(7):1160-1168.
Spoth, et al., AJPM 2011;40(4):440-447
For 100 young adults
in general population
starting Rx abuse,
only 35 young adults
from an intervention
community started.
Overall, three studies
now suggest the
impact of universal
prevention on
prescription drug
abuse.

38. www.drugabuse.gov

39. Numbers
in
Thousands
Source:
2011
Na2onal
Survey
on
Drug
Use
and
Health,
SAMHSA,
2012.
Large Number of Past Year Initiates of Pharmaceuticals:
Persons Aged 12 or Older, 2011
Marijuana
Pain Relievers
Tranquilizers
Ecstasy
Inhalants
Cocaine
Stimulants
LSD
Heroin
Sedatives
PCP

40. Overdoses of prescription painkillers
have more than tripled in the past 20
years, killing more than 15,500 people in
the US in 2009
For
every
overdose
death
from
prescrip=on
painkillers
there
are
treatment
admissions
for
abuse
emergency
department
visits
for
misuse
or
abuse
people
who
abuse
or
are
dependent
people
who
take
prescrip=on
painkillers
for
non-­‐medical
use
10
32
130
825